Research Paper Volume 13, Issue 12 pp 16667—16683
Correlation of IL-6 and JAK2/STAT3 signaling pathway with prognosis of nasopharyngeal carcinoma patients
- 1 Department of Oncology, The Fourth People’s Hospital of Jinan, Jinan 250031, PR China
- 2 Department of Oncology, Jinan Fuda Cancer Hospital, Jinan 250033, PR China
- 3 Department of Clinical Laboratory, The Fourth People’s Hospital of Jinan, Jinan 250031, PR China
- 4 Department of Radiation Neurology, The Fourth People’s Hospital of Jinan, Jinan 250031, PR China
- 5 Department of Radiation Oncology, The Fourth People’s Hospital of Jinan, Jinan 250031, PR China
- 6 School of Graduate Studies, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 271099, PR China
- 7 Department of Radiation Oncology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical of Guangzhou University of Chinese Medicine, Shenzhen 518033, PR China
- 8 Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, PR China
Received: December 23, 2020 Accepted: May 24, 2021 Published: June 22, 2021
https://doi.org/10.18632/aging.203186How to Cite
Copyright: © 2021 Zhuang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
IL-6 is reported to be the main upstream activator, instead of the downstream target of JAK2/STAT3. This study is intended to explore the correlation of IL-6 and JAK2/STAT3 signaling pathway with clinicopathological features and prognosis in nasopharyngeal carcinoma (NPC). First, NPC tissues and normal nasopharyngeal epithelial tissues were obtained from 117 NPC patients. Next, we detected expression levels of IL-6 in serum and those of STAT3, p-STAT3, JAK2, p-JAK2 and CyclinD1 in tissues. A follow-up was conducted in all the patients and the survival was analyzed. To verify the correlation of IL-6 and JAK2/STAT3 pathway, CNE-1 and SUNE1 NPC cells were interpreted with IL-6 and JAK2/STAT3 signaling pathway inhibitor AG490 to detect cell viability, migration and invasion. We observed thatIL-6 increased in serum of NPC patients. The expressions of IL-6, STAT3, p-STAT3, JAK2, p-JAK2 and CyclinD1 in NPC tissues were higher and correlated with TNM stage and lymph node metastasis (LNM). Survival rates were reduced in patients with positive expressions of IL-6, STAT3, p-STAT3, JAK2, p-JAK2 and CyclinD1. LNM and positive expressions of IL-6 and p-STAT3 were risk factors for poor prognosis of NPC. Besides, recombinant human IL-6 promoted cell proliferation, invasion and migration while AG490 inhibited cell proliferation, invasion and migration in CNE-1 and SUNE1 NPC cells. The results demonstrated that increased IL-6 expression and the activated JAK2/STAT3 signaling pathway had effects on prognosis and reduced the survival time in NPC patients, which provide a potential target for the treatment of NPC.
Abbreviations
NPC: nasopharyngeal carcinoma; gp130: glycoprotein 130; JAK/STAT: Janus-activated kinase signal transducer and activator of transcription; WHO: World Health Organization; TNM: tumor node metastasis; LNM: lymph node metastasis; OD: optical density; ELISA: Enzyme-linked immunosorbent assay; IHC: Immunohistochemistry; PBS: phosphate-buffered saline; DAB: diaminobenzidine; RT-qPCR: Reverse transcription quantitative polymerase chain reaction; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; SDS-PAGE: sulfate-polyacrylamide gel electrophoresis; FBS: fetal bovine serum; CCK-8: Cell counting kit-8 assay.